The primary objective of this study is to determine the recommended phase 2 dose (RP2D) and characterize the safety profile of TG-1801. As per protocol v3.0, ublituximab will be discontinued.

Start Date28 Apr 2021

Sponsor / Collaborator

TG Therapeutics, Inc.

NCT03804996 / CompletedPhase 1

A Phase 1 First-in-Human Study of Bispecific Antibody TG-1801 in Subjects With B-Cell Lymphoma

Phase 1 first in human Study to Assess the Bispecific Antibody TG-1801 in Subjects with B-Cell Lymphoma

Start Date05 Mar 2019

Sponsor / Collaborator

TG Therapeutics, Inc.

100 Clinical Results associated with TG-1801

100 Translational Medicine associated with TG-1801

100 Patents (Medical) associated with TG-1801

Literatures (Medical) associated with TG-1801

01 Jan 2023·Frontiers in immunology

G protein-coupled receptor 183 mediates the sensitization of Burkitt lymphoma tumors to CD47 immune checkpoint blockade by anti-CD20/PI3Kδi dual therapy.

Article

Author: Normant, Emmanuel ; Roué, Gael ; Ribeiro, Marcelo Lima ; Bosch, Francesc ; Fernández-Serrano, Miranda ; Reyes-Garau, Diana ; Esteller, Manel ; Profitós-Pelejà, Núria ; Miskin, Hari P ; Armengol, Marc ; Santos, Juliana Carvalho ; Blecua, Pedro

Immunotherapy-based regimens have considerably improved the survival rate of B-cell non-Hodgkin lymphoma (B-NHL) patients in the last decades; however, most disease subtypes remain almost incurable.TG-1801, a bispecific antibody that targets CD47 selectively on CD19+ B-cells, is under clin. evaluation in relapsed/refractory (R/R) B-NHL patients either as a single-agent or in combination with ublituximab, a new generation CD20 antibody.A set of eight B-NHL cell lines and primary samples were cultured in vitro in the presence of bone marrow-derived stromal cells, M2-polarized primary macrophages, and primary circulating PBMCs as a source of effector cells.Cell response to TG-1801 alone or combined with the U2 regimen associating ublituximab to the PI3Kδ inhibitor umbralisib, was analyzed by proliferation assay, western blot, transcriptomic anal. (qPCR array and RNA sequencing followed by gene set enrichment anal.) and/or quantification of antibody-dependent cell death (ADCC) and antibody-dependent cell phagocytosis (ADCP).CRISPR-Cas9 gene edition was used to selectively abrogate GPR183 gene expression in B-NHL cells.In vivo, drug efficacy was determined in immunodeficient (NSG mice) or immune-competent (chicken embryo chorioallantoic membrane (CAM)) B-NHL xenograft models.Using a panel of B-NHL co-cultures, we show that TG-1801, by disrupting the CD47-SIRPa axis, potentiates anti-CD20-mediated ADCC and ADCP.This led to a remarkable and durable antitumor effect of the triplet therapy composed by TG-1801 and U2 regimen, in vitro, as well as in mice and CAM xenograft models of B-NHL.Transcriptomic anal. also uncovered the upregulation of the G protein-coupled and inflammatory receptor, GPR183, as a crucial event associated with the efficacy of the triplet combination.Genetic depletion and pharmacol. inhibition of GPR183 impaired ADCP initiation, cytoskeleton remodeling and cell migration in 2D and 3D spheroid B-NHL cocultures, and disrupted macrophage-mediated control of tumor growth in BNHL CAM xenografts.Altogether, our results support a crucial role for GPR183 in the recognition and elimination of malignant B cells upon concomitant targeting of CD20, CD47 and PI3Kδ, and warrant further clin. evaluation of this triplet regimen in B-NHL.

01 Dec 2022·Experimental Hematology & OncologyQ3 · MEDICINE

CD47xCD19 bispecific antibody triggers recruitment and activation of innate immune effector cells in a B-cell lymphoma xenograft model

Q3 · MEDICINE

ArticleOA

Author: Shang, Limin ; Masternak, Krzysztof ; Moine, Valéry ; Pontini, Guillemette ; Chatel, Laurence ; Daubeuf, Bruno ; Chollet, Didier ; Didelot, Gérard ; Chauchet, Xavier ; Buatois, Vanessa ; Cons, Laura ; Malinge, Pauline ; Ferlin, Walter

AbstractBackgroundCD47/SIRPα axis is recognized as an innate immune checkpoint and emerging clinical data validate the interest of interrupting this pathway in cancer, particularly in hematological malignancies. In preclinical models, CD47/SIRPα blocking agents have been shown to mobilize phagocytic cells and trigger adaptive immune responses to eliminate tumors. Here, we describe the mechanisms afforded by a CD47xCD19 bispecific antibody (NI-1701) at controlling tumor growth in a mouse xenograft B-cell lymphoma model.MethodsThe contribution of immune effector cell subsets behind the antitumor activity of NI-1701 was investigated using flow cytometry, transcriptomic analysis, and in vivo immune-cell depletion experiments.ResultsWe showed that NI-1701 treatment transformed the tumor microenvironment (TME) into a more anti-tumorigenic state with increased NK cells, monocytes, dendritic cells (DC) and MHCIIhi tumor-associated macrophages (TAMs) and decreased granulocytic myeloid-derived suppressor cells. Notably, molecular analysis of isolated tumor-infiltrating leukocytes following NI-1701 administration revealed an upregulation of genes linked to immune activation, including IFNγ and IL-12b. Moreover, TAM-mediated phagocytosis of lymphoma tumor cells was enhanced in the TME in the presence of NI-1701, highlighting the role of macrophages in tumor control. In vivo cell depletion experiments demonstrated that both macrophages and NK cells contribute to the antitumor activity. In addition, NI-1701 enhanced dendritic cell-mediated phagocytosis of tumor cells in vitro, resulting in an increased cross-priming of tumor-specific CD8 T cells.ConclusionsThe study described the mechanisms afforded by the CD47xCD19 bispecific antibody, NI-1701, at controlling tumor growth in lymphoma mouse model. NI-1701 is currently being evaluated in a Phase I clinical trial for the treatment of refractory or relapsed B-cell lymphoma (NCT04806035).

01 Aug 2018·Molecular Cancer TherapeuticsQ2 · MEDICINE

Preclinical Development of a Bispecific Antibody that Safely and Effectively Targets CD19 and CD47 for the Treatment of B-Cell Lymphoma and Leukemia

Q2 · MEDICINE

Article

Author: D'Asaro, Matilde ; Eissenberg, Linda ; Kosco-Vilbois, Marie H. ; Broyer, Lucile ; Bailey, Katharine ; Johnson, Zoë ; Ritchey, Julie ; Barba, Leticia ; Daubeuf, Bruno ; Masternak, Krzysztof ; Buatois, Vanessa ; LeGallou, Simon ; Fest, Thierry ; Clarke Hinojosa, Robert K. ; Tarte, Karin ; Chauchet, Xavier ; Fischer, Nicolas ; DiPersio, John F. ; Dey, Aditi ; Matthes, Thomas ; Hatterer, Eric ; Salgado-Pires, Susana ; Papaioannou, Anne ; Ribera, José María ; Shang, Limin ; Genescà Ferrer, Eulàlia ; Rettig, Michael ; Fielding, Adele K. ; Cons, Laura ; Richard, Françoise ; Ferlin, Walter G.

AbstractCD47, an ubiquitously expressed innate immune checkpoint receptor that serves as a universal “don't eat me” signal of phagocytosis, is often upregulated by hematologic and solid cancers to evade immune surveillance. Development of CD47-targeted modalities is hindered by the ubiquitous expression of the target, often leading to rapid drug elimination and hemotoxicity including anemia. To overcome such liabilities, we have developed a fully human bispecific antibody, NI-1701, designed to coengage CD47 and CD19 selectively on B cells. NI-1701 demonstrates favorable elimination kinetics with no deleterious effects seen on hematologic parameters following single or multiple administrations to nonhuman primates. Potent in vitro and in vivo activity is induced by NI-1701 to kill cancer cells across a plethora of B-cell malignancies and control tumor growth in xenograft mouse models. The mechanism affording maximal tumor growth inhibition by NI-1701 is dependent on the coengagement of CD47/CD19 on B cells inducing potent antibody-dependent cellular phagocytosis of the targeted cells. NI-1701–induced control of tumor growth in immunodeficient NOD/SCID mice was more effective than that achieved with the anti-CD20 targeted antibody, rituximab. Interestingly, a synergistic effect was seen when tumor-implanted mice were coadministered NI-1701 and rituximab leading to significantly improved tumor growth inhibition and regression in some animals. We describe herein, a novel bispecific antibody approach aimed at sensitizing B cells to become more readily phagocytosed and eliminated thus offering an alternative or adjunct therapeutic option to patients with B-cell malignancies refractory/resistant to anti-CD20–targeted therapy. Mol Cancer Ther; 17(8); 1739–51. ©2018 AACR.

News (Medical) associated with TG-1801

16 Jan 2021

·www.globenewswire.com

TG Therapeutics to Participate in the B. Riley Securities Oncology Investor Conference

NEW YORK, Jan. 15, 2021 (GLOBE NEWSWIRE) -- TG Therapeutics, Inc. (NASDAQ: TGTX), today announced that Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer, will participate in a fireside chat during the B. Riley Securities Oncology Investor Conference being held virtually. The fireside chat is scheduled to take place on Wednesday, January 20, 2021 at 10:00 AM ET. A live webcast of this presentation will be available on the Events page, located within the Investors & Media section, of the Company’s website at . A replay of the webcast will be available on TG’s website following the event. ABOUT TG THERAPEUTICS, INC. TG Therapeutics is a biopharmaceutical company focused on the acquisition, development and commercialization of novel treatments for B-cell malignancies and autoimmune diseases. Currently, the company is developing multiple therapies targeting hematological malignancies and autoimmune diseases. Ublituximab (TG-1101) is a novel, glycoengineered monoclonal antibody that targets a specific and unique epitope on the CD20 antigen found on mature B-lymphocytes. TG Therapeutics is also developing umbralisib (TGR-1202), an oral, once-daily dual inhibitor of PI3K-delta and CK1-epsilon. Umbralisib is currently under review by the U.S. Food and Drug Administration (FDA) for accelerated approval as a treatment for patients with previously treated marginal zone lymphoma (MZL) who have received at least one prior anti-CD20 based regimen or follicular lymphoma (FL) who have received at least two prior systemic therapies. Both ublituximab and umbralisib, or the combination of which is referred to as "U2", are in Phase 3 clinical development for patients with hematologic malignancies, with ublituximab also in Phase 3 clinical development for Multiple Sclerosis. Additionally, the Company has recently brought into Phase 1 clinical development its anti-PD-L1 monoclonal antibody, cosibelimab (TG-1501), its Bruton’s Tyrosine Kinase (BTK) inhibitor, TG-1701, as well as its anti-CD47/CD19 bispecific antibody, TG-1801. TG Therapeutics is headquartered in New York City. CONTACT: Jenna Bosco Senior Vice President, Corporate Communications TG Therapeutics, Inc. Telephone: 212.554.4351 Email: ir@tgtxinc.com

AntibodyAccelerated ApprovalAcquisition

08 Jan 2021

·www.biospace.com

TG Therapeutics to Present at the 39th Annual J.P. Morgan Healthcare ConferencePresentation scheduled for Tuesday, January 12, 2021 at 2:00 PM ET

NEW YORK, Jan. 08, 2021 (GLOBE NEWSWIRE) -- TG Therapeutics, Inc., Inc. (NASDAQ: TGTX) today announced that Michael S. Weiss, the Company’s Executive Chairman and Chief Executive Officer, will present at the 39th Annual J.P. Morgan Healthcare Conference, being held virtually. The presentation is scheduled to take place on Tuesday, January 12, 2021 at 2:00 PM ET. A live webcast of this presentation will be available on the Events page, located within the Investors & Media section, of the Company’s website at . A replay of the webcast will be available on TG’s website following the event. ABOUT TG THERAPEUTICS, INC. TG Therapeutics is a biopharmaceutical company focused on the acquisition, development and commercialization of novel treatments for B-cell malignancies and autoimmune diseases. Currently, the company is developing multiple therapies targeting hematological malignancies and autoimmune diseases. Ublituximab (TG-1101) is a novel, glycoengineered monoclonal antibody that targets a specific and unique epitope on the CD20 antigen found on mature B-lymphocytes. TG Therapeutics is also developing umbralisib (TGR-1202), an oral, once-daily dual inhibitor of PI3K-delta and CK1-epsilon. Umbralisib is currently under review by the U.S. Food and Drug Administration (FDA) for accelerated approval as a treatment for patients with previously treated marginal zone lymphoma (MZL) who have received at least one prior anti-CD20 based regimen or follicular lymphoma (FL) who have received at least two prior systemic therapies. Both ublituximab and umbralisib, or the combination of which is referred to as "U2", are in Phase 3 clinical development for patients with hematologic malignancies, with ublituximab also in Phase 3 clinical development for Multiple Sclerosis. Additionally, the Company has recently brought into Phase 1 clinical development its anti-PD-L1 monoclonal antibody, cosibelimab (TG-1501), its Bruton’s Tyrosine Kinase (BTK) inhibitor, TG-1701, as well as its anti-CD47/CD19 bispecific antibody, TG-1801. TG Therapeutics is headquartered in New York City. CONTACT: Jenna A. Bosco Senior Vice President, Corporate Communications TG Therapeutics, Inc. Telephone: 212.554.4351 Email: ir@tgtxinc.com

AntibodyAccelerated ApprovalAcquisition

100 Deals associated with TG-1801

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
B-Cell Malignant Neoplasm	Phase 1	CH	Novimmune SA	30 Jan 2022
B-Cell Malignant Neoplasm	Phase 1	CH	TG Therapeutics, Inc.	30 Jan 2022
B-Cell Lymphoma	Phase 1	AU	TG Therapeutics, Inc.	05 Mar 2019
Chronic Lymphocytic Leukemia	Preclinical	US	TG Therapeutics, Inc.	28 Apr 2021
Follicular Lymphoma	Preclinical	US	TG Therapeutics, Inc.	28 Apr 2021
Mantle-Cell Lymphoma	Preclinical	US	TG Therapeutics, Inc.	28 Apr 2021
Marginal Zone B-Cell Lymphoma	Preclinical	US	TG Therapeutics, Inc.	28 Apr 2021
Mediastinal large B-cell lymphoma	Preclinical	US	TG Therapeutics, Inc.	28 Apr 2021
Small Lymphocytic Lymphoma	Preclinical	US	TG Therapeutics, Inc.	28 Apr 2021

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT03804996 (FIH Study of TG-1801, ICML2023)	Phase 1	B-Cell Lymphoma CD19+ \| CD47	30	TG-1801 monotherapy	(yyqsakequi) = tiuyuzoiri rgijewmuvp (wmtdnsvlhk )	Positive	09 Jun 2023
				TG-1801 + ublituximab combination therapy	(tufxhwxaen) = xsrrfokmvc ewkdxieilq (nwkltqpilw ) View more
NCT03804996 (ASH2022) Manual	Phase 1	B-Cell Lymphoma	30	TG-1801	(tbnlmtzxql) = 1 infusion reaction [500 mg monotherapy], 1 rash [360 mg monotherapy] pxoegpbxkv (pwdhtgpyxu ) View more	Positive	11 Dec 2022
				TG-1801+ublituximab

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